H. Iyehara Ogawa

Genotoxic activities in vivo of cobaltous chloride and other metal chlorides as assayed in the Drosophila wing spot test.

A series of metal chlorides were subjected to the wing spot test of Drosophila melanogaster. In the test, larvae trans-heterozygous for the wing-hair mutations mwh and flr were orally treated at the third instar stage with a test compound and the wings were inspected at the adult stage for spots expressing phenotypes of the markers. CoCl2, MnCl2, MoCl3, NiCl2 and ZnCl2 were clearly effective in inducing spots with one or two mutant hairs (small spots). CoCl2 was clearly effective in inducing spots with three or more mutant hairs (large spots) as well. CrCl3, FeCl2 and FeCl3 were negative under the conditions used. Based on estimated frequencies of small spots induced at the LD50, the genotoxic effectiveness of the positive metal salts were ranked in a sequence of CoCl2 > ZnCl2 > MoCl3 > (MnCl2, NiCl2). Since CoCl2 did not induce large spots in the wings of the mwh/TM3 flies with a suppressed ability of mitotic crossing-over, the large spots induced by this compound in the mwh/flr system were ascertained as mutant clones due to mitotic crossing-overs.

Mutagenicity of various chemicals including nickel and cobalt compounds in cultured mouse fm3a cells

Employing a suspension culture of FM3A cells, we examined the cytotoxic and mutagenic effects of various chemical compounds. Mutagenicity of various types of mutagens (MNNG, ENNG, sterigmatocystin, mitomycin C, Trp-P-1, and X-rays) was sensitively detected by this assay. Mutagenicity of Trp-P-2 was detected in the presence of an activating enzyme system. Nickel(II) and cobalt(II) compounds (NiCl2, Ni(CH3COO)2, nickel complex [(C2H5)4N]2 [NiCl4], CoCl2, and a cobalt complex [(C2H5)4N]2-[CoCl4]) were cytotoxic to FM3A cells at concentrations of over 1 X 10(-4) M, and produced 2-6-fold increases of the control in the average number of 6-thioguanine-resistant (6TGr) colonies over a very narrow concentration range of 2-4 X 10(-4) M. Comparison of the mutagenicity of various chemical compounds suggested that some of the nickel(II) and cobalt(II) compounds were very weak mutagens.

Combined mutagenicity of cobalt(II) salt and heteroaromatic compounds in Salmonella typhimurium.

Mutagenic activities of 4-aminopyridine (4AP), 4-aminoquinoline (4AQ), 9-aminoacridine (9AA) and harman (HM) were examined by the Salmonella test system in the presence of cobalt(II) chloride (CoCl2), which itself is non-mutagenic in this system. Mutagenic activity of the mixture of 9AA and CoCl2 was found to be much higher than that of 9AA alone in strains TA1537 and TA2637. A similar enhancing phenomenon was observed in 4AQ-CoCl2 and HM-CoCl2 mixtures but not in that of 4AP-CoCl2. Judging from visible and nuclear magnetic resonance spectral data, this increased mutagenicity may be attributable to the formation of moderate to weak complexes between these chemicals and the Co(II) cation. A survey of the mutagenicity of several Co(II) complexes supported this interpretation.

Preparation and characterization of cobalt(II), nickel(II) and copper(II) complexes with water-soluble macrocyclic N4-ligands: 6,15-diethyl-4,13-dihydro-1,10-dimethyl-(E)-dipyridinio [b,i] [1,4,8,11] tetraazacyclotetradecine iodide or methyl sulfate

Abstract The mixture of 6,15-diethyl-4,13-dihydro-( E )-dipyrido [b,i] [1,4,8,11] tetraazacyclotetradecine ( 2-E ) and 6,15-diethyl-4,13-dihydro-( Z )-dipyrido [b,i][1,4,8,11] tetraazacyclotetradecine ( 2-Z ) was prepared by cyclization of 3,4-diaminopyridine and 2-ethyl-3-ethoxyacrolein. Two kinds of isomers were separated by repeated recrystallization from chloroform. Methylation of pyridine comprised in 2-E using iodomethane or dimethyl sulfate afforded the corresponding dimethylated product ( 2-E-I or 2-E-S ), which is soluble in water. The cobalt(II), nickel(II) and copper(II) complexes of 2-E-I and 2-E-S were prepared. The absorption bands appearing in the energy range greater than 18 000 cm −1 were attributed to the π → π* transitions within a ligand molecule and CT transitions from metal to ligand. Since the d → d* bands for nickel(II) and copper(II) complexes were obscured by the π → π* and CT bands, no significant absorption bands were found in the region more than 18000 cm −1 . One of the d → d* bands for the cobalt(II) complex was observed at around 13 000 cm −1 . These complexes assume the square- planar structures. A strong IR band due to the CN stretching mode of the macrocycle moiety was observed at ca. 1640 cm −1 and shifted slightly toward lower energy upon metal-coordination, cis ( 2-Z ) and trans ( 2-E ) isomers in the present macrocycle can be judged by the amine proton signals of NMR spectra. All proton signals except for amine protons show downfield shifts due to the deshielding effect of the positive charge provided by methylation of pyridine contained in the metal-free macrocycle. Upon formation of the nickel(II) complex all proton signals, except the aromatic protons adjacent to the nitrogen atom of a pyridine ring, also show a downfield shift, which is attributed to the deshielding effect based on the positive charge given by nickel(II). The intensity change of the electronic spectrum at 425 nm is available for the determination of copper(II) concentrations in the aqueous solution using the water-soluble macrocycles ( 2-E-I and 2-E-S ) and a good linear correlation is observed up to 8 × 10 −6 mol dm −3 .

Inverse correlation between combined mutagenicity in Salmonella typhimurium and strength of coordinate bond in mixtures of cobalt(II) chloride and 4-substituted pyridines

Cobalt(II) chloride (CoCl2), non-mutagenic by itself, has been tested for mutagenic activity in the presence of 4-substituted pyridines in the test strains of Salmonella typhimurium. CoCl2 was found to be mutagenic in strains TA1537 and TA2637, when combined pyridine, with methyl isonicotinate, 4-methyl-pyridine, 4-ethylpyridine, 4-chloropyridine or 4-bromopyridine. Mixtures of CoCl2 and isonicotinic acid, 4-cyanopyridine, 4-aminopyridine, or 4-dimethylaminopyridine exhibited no mutagenicity. Judging from the spectral observations, such combined mutagenicity may be due to the formation of moderate to weak complexes between these compounds and the Co(II) cation.

Preparation and Characterization of Zinc(II) and Palladium(II) Complexes with Dipyrido[14]Annulenes

Abstract The reaction of 5, 14-dihydro-7, 16-diethyl-(E)-or-(Z)-di-pyrido[b,i][1,4,8,11]tetraazacyclotetradecine with bis(2,4-pen-tanedionato)aquazinc(II) led to the corresponding zinc(II) mono-hydrate complexes, while the reaction with sodium tetrachloro-palladate(II) yielded the corresponding palladium(II) complexes. Judging from the behavior of electronic and 1H-n.m.r. spectra, the zinc(II) complexes are presumed to exist in aggregate species in a relatively high concentration range. Mass, i.r., u.v.-visible, and 13C-n.m.r. data are also presented.